It has been demonstrated with indirect methods of evaluating the changes in the extent of the infarction that several interventions may modify infarct size following an experimental acute coronary occlusion. However, these studies have not provided a quantitative assessment of the effects of these interventions on the actual size of an acute myocardial infarction. The goal of the present proposal is to study the effects of drugs on the actual size of acute myocardial infarction induced by coronary artery occlusion in rats. This approach offers the following advantages: 1. The variability in size the infarctions, when determined histologically, is relatively small. 2. By studying the size of an infarct both by its histological appearance, and total left ventricular creatine phosphokinase (CPK) activity, the total size of the infarction can be determined directly. Evaluation of the total extent of necrosis, both by histology and by myocardial CPK activity, will strengthen the reliability of the conclusions. 3. The surgical technique, once learned, permits experiments on large numbers of animals in a brief period of time, thus allowing more rapid and more efficient study of the effects of an intervention than is possible using models based on large animals. Pilot experiments have demonstrated that the technique of coronary artery occlusion in the rat can be easily performed and that the extent of myocardial necrosis can be assessed precisely and reproducibly using histological techniques and myocardial CPK activity. The variability in the extent of infarcts in the pilot experiments was small and it could readily be demonstrated that hyaluronidase reduced infarct size considerably. In the present study it is proposed to determine the influence of hyaluronidase, glucocorticoids, propranolol, aprotinin and cobra venom factor in infarct size; to verify whether any combination of these drugs have additive or synergistic effects; to demonstrate the time following coronary artery occlusion during which these interventions are effective and the duration of time that they have to be applied in order to exert their effects.